8e0q: Difference between revisions
New page: '''Unreleased structure''' The entry 8e0q is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==Structure of the human UBR5 HECT-type E3 ubiquitin ligase in a C2 symmetric dimeric form== | ||
<StructureSection load='8e0q' size='340' side='right'caption='[[8e0q]], [[Resolution|resolution]] 2.66Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8e0q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E0Q FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.66Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8e0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e0q OCA], [https://pdbe.org/8e0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e0q RCSB], [https://www.ebi.ac.uk/pdbsum/8e0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e0q ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/UBR5_HUMAN UBR5_HUMAN] E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (By similarity). Involved in maturation and/or transcriptional regulation of mRNA by activating CDK9 by polyubiquitination. May play a role in control of cell cycle progression. May have tumor suppressor function. Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response. Plays an essential role in extraembryonic development. Ubiquitinates acetylated PCK1. Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes.<ref>PMID:21127351</ref> <ref>PMID:21726808</ref> <ref>PMID:22884692</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The human UBR5 is a single polypeptide chain homology to E6AP C terminus (HECT)-type E3 ubiquitin ligase essential for embryonic development in mammals. Dysregulated UBR5 functions like an oncoprotein to promote cancer growth and metastasis. Here, we report that UBR5 assembles into a dimer and a tetramer. Our cryoelectron microscopy (cryo-EM) structures reveal that two crescent-shaped UBR5 monomers assemble head to tail to form the dimer, and two dimers bind face to face to form the cage-like tetramer with all four catalytic HECT domains facing the central cavity. Importantly, the N-terminal region of one subunit and the HECT of the other form an "intermolecular jaw" in the dimer. We show the jaw-lining residues are important for function, suggesting that the intermolecular jaw functions to recruit ubiquitin-loaded E2 to UBR5. Further work is needed to understand how oligomerization regulates UBR5 ligase activity. This work provides a framework for structure-based anticancer drug development and contributes to a growing appreciation of E3 ligase diversity. | |||
Structure of the human UBR5 E3 ubiquitin ligase.,Wang F, He Q, Zhan W, Yu Z, Finkin-Groner E, Ma X, Lin G, Li H Structure. 2023 May 4;31(5):541-552.e4. doi: 10.1016/j.str.2023.03.010. Epub 2023 , Apr 10. PMID:37040767<ref>PMID:37040767</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8e0q" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: He Q]] | |||
[[Category: Li H]] | |||
[[Category: Lin G]] | |||
[[Category: Wang F]] | |||
Latest revision as of 08:23, 12 June 2024
Structure of the human UBR5 HECT-type E3 ubiquitin ligase in a C2 symmetric dimeric formStructure of the human UBR5 HECT-type E3 ubiquitin ligase in a C2 symmetric dimeric form
Structural highlights
FunctionUBR5_HUMAN E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (By similarity). Involved in maturation and/or transcriptional regulation of mRNA by activating CDK9 by polyubiquitination. May play a role in control of cell cycle progression. May have tumor suppressor function. Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response. Plays an essential role in extraembryonic development. Ubiquitinates acetylated PCK1. Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes.[1] [2] [3] Publication Abstract from PubMedThe human UBR5 is a single polypeptide chain homology to E6AP C terminus (HECT)-type E3 ubiquitin ligase essential for embryonic development in mammals. Dysregulated UBR5 functions like an oncoprotein to promote cancer growth and metastasis. Here, we report that UBR5 assembles into a dimer and a tetramer. Our cryoelectron microscopy (cryo-EM) structures reveal that two crescent-shaped UBR5 monomers assemble head to tail to form the dimer, and two dimers bind face to face to form the cage-like tetramer with all four catalytic HECT domains facing the central cavity. Importantly, the N-terminal region of one subunit and the HECT of the other form an "intermolecular jaw" in the dimer. We show the jaw-lining residues are important for function, suggesting that the intermolecular jaw functions to recruit ubiquitin-loaded E2 to UBR5. Further work is needed to understand how oligomerization regulates UBR5 ligase activity. This work provides a framework for structure-based anticancer drug development and contributes to a growing appreciation of E3 ligase diversity. Structure of the human UBR5 E3 ubiquitin ligase.,Wang F, He Q, Zhan W, Yu Z, Finkin-Groner E, Ma X, Lin G, Li H Structure. 2023 May 4;31(5):541-552.e4. doi: 10.1016/j.str.2023.03.010. Epub 2023 , Apr 10. PMID:37040767[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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